In silico Molecular Docking Analysis of Stephania glabra phytocompounds Targeting Thymidylate Kinase for potential Antituberculosis Activity

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Open Access

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Notice

nThis is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.n

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Year : 2025 [if 2224 equals=””]29/08/2025 at 2:30 PM[/if 2224] | [if 1553 equals=””] Volume : 03 [else] Volume : [/if 1553] | [if 424 equals=”Regular Issue”]Issue : [/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424] 02 | Page :

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    By

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    Sandeep Chandaragi,

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  1. Student, Bionome (CRO), Karnataka, India

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Abstract

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nTuberculosis (TB) is an infectious disease caused by the bacteria Mycobacterium
tuberculosis. It mainly affects the lungs and spreads through the air when a person with active
TB in their lungs coughs, sneezes, or spits. This study investigates several bioactive
compounds derived from plants to forecast how effective plant-based ligands will be at
preventing tuberculosis. The purpose of the study was to use computational techniques to
assess the effectiveness of several phytochemicals against the Mycobacterium. Molecular
docking was systematically carried out using the virtual screening software PyRx. The top 5
phytocompounds from Stephania glabra were chosen among them to test their compatibility
with the thymidylate protein 5NR7, using the ADMET filters, the ligands pharmacological
evaluation was performed. The phytocompounds Roemerine, Stepholidine,
Tetrahydropalmatine, Rotundine, Corydalmine from the plant Stephania glabra were
discovered to be the most potent antagonist for the protein Thymidylate kinase. All of the
bioactive chemicals could be considered as deserving candidates for the suppression of
tuberculosis due to their strong affinity for the protein. Among the top ligand the
phytoconstituent Roemerine demonstrated better binding affinity with target.nn

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Keywords: Adenosine triphosphate (ATP), Blood-Brain Barrier (BBB), C-type lectin receptors (CLRs), Gastrointestinal absorption (GI), Mycobacterium tuberculosis (Mtb), Molecular Doching (MD), Nod-like receptors (NLRs), Stephania Glabra, Toll-Like receptors (TLRs), Thymidylate kinase (TMK), Thymidine monophosphate (dTMP), Thymidine diphosphate (dTDP), Thymidine -5’triphosphate (dTTP), Tuberculosis (TB)

n[if 424 equals=”Regular Issue”][This article belongs to International Journal of Molecular Biotechnological Research ]

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[/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in International Journal of Molecular Biotechnological Research (ijmbr)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

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How to cite this article:
nSandeep Chandaragi. [if 2584 equals=”][226 wpautop=0 striphtml=1][else]In silico Molecular Docking Analysis of Stephania glabra phytocompounds Targeting Thymidylate Kinase for potential Antituberculosis Activity[/if 2584]. International Journal of Molecular Biotechnological Research. 29/08/2025; 03(02):-.

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How to cite this URL:
nSandeep Chandaragi. [if 2584 equals=”][226 striphtml=1][else]In silico Molecular Docking Analysis of Stephania glabra phytocompounds Targeting Thymidylate Kinase for potential Antituberculosis Activity[/if 2584]. International Journal of Molecular Biotechnological Research. 29/08/2025; 03(02):-. Available from: https://journals.stmjournals.com/ijmbr/article=29/08/2025/view=0

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References n

n[if 1104 equals=””]n

1. Lam A, Prabhu R, Gross CM, Riesenberg LA, Singh V, Aggarwal S. Role of
apoptosis and autophagy in tuberculosis. Am J Physiol Lung Cell Mol Physiol.
2017;313(2):L218–29.

2. Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, et al. Tuberculosis.
Nat Rev Dis Primers. 2016;2:16076.

3. Raja A. Immunology of tuberculosis. Indian J Med Res. 2004;120(4):213–32.

4. Mortaz E, Adcock IM, Tabarsi P, Masjedi MR, Mansouri D, Velayati AA, et al.
Interaction of pattern recognition receptors with Mycobacterium tuberculosis. J Clin
Immunol. 2015;35(1):1–10.

5. Jayanthi K, Azam MA. Thymidylate kinase inhibitors as antibacterial agents: A
review. Appl Biochem Microbiol. 2023;59(3):250–66.

6. Cui WS, Shin Y, Luo J, Tian H, Cui DY. Thymidylate kinase: an old topic brings new
perspectives. Curr Med Chem. 2013;20(10):1281–92.

7. Sukumar S, Krishnan A, Khan MKA. Protein kinases as antituberculosis targets: the
case of thymidylate kinases. Front Biosci (Landmark Ed). 2020;25:1042–55.

8. Owono Owono LC, Keita M, Megnassan E, Frecer V, Miertus S. Design of thymidine
analogues targeting thymidylate kinase of Mycobacterium tuberculosis. Tuberc Res
Treat. 2013;2013:670836.

9. Shahab M, Danial M, Duan X, Khan T, Liang C, Gao H, et al. Machine learning-
based drug design for identification of thymidylate kinase inhibitors as potential anti-
Mycobacterium tuberculosis. J Biomol Struct Dyn. 2023.
doi:10.1080/07391102.2023.2216278.

19
10. Song L, Merceron R, Hulpia F, Lucía A, Gracia B, Jian Y, et al. Structure-aided
optimization of non-nucleoside M. tuberculosis thymidylate kinase inhibitors. Eur J
Med Chem. 2021;218:113784.

11. Tuang KL, Min HM, Sein MM. Extraction, isolation, antimicrobial study and
structural elucidation of a pure compound isolated from the tuber of Stephania glabra
(Roxb.) Miers. [Journal name and volume/issue/page not provided—please complete.]

12. Semwal DK, Semwal RB. Efficacy and safety of Stephania glabra: an alkaloid-rich
traditional medicinal plant. Nat Prod Res. 2014;29(5):396–410.

13. Duke JA. Handbook of phytochemical constituents of GRAS herbs and other
economic plants. Boca Raton (FL): CRC Press; 1992.

14. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2025 update.
Nucleic Acids Res. 2025;53(D1):D1516–25.

15. Song L, Merceron R, Gracia B, Quintana AL, Risseeuw MDP, Hulpia F, et al. J Med
Chem. 2018;61(7):2753–75.

16. Jejurikar BL, Rohane SH. Drug designing in discovery studio. Asian J Res Chem.
2021;14(2):135–8.

17. Zhou AQ, O’Hern CS, Regan L. Revisiting the Ramachandran plot from a new angle.
Protein Sci. 2011;20(7):1166–71.

18. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate
pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small
molecules. Sci Rep. 2017;7:42717.

19. Yang H, Lou C, Sun L, Li J, Cai Y, Wang Z, et al. ADMETsar 2.0: web-service for
prediction and optimization of chemical ADMET properties. Bioinformatics.
2019;35(6):1067–9.

20. Kondapuram SK, Sarvagalla S, Coumar MS. Docking-based virtual screening using
PyRx tool: autophagy target Vps34 as a case study. In: Molecular Docking for
Computer-Aided Drug Design. Amsterdam: Elsevier Inc.; 2021. p. 463–77.

21. Tobin EH, Tristram D. Tuberculosis overview. [Updated 2024 Dec 22]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK441916/

22. Warner DF, Koch A, Mizrahi V. Diversity and disease pathogenesis in Mycobacterium
tuberculosis. Trends Microbiol. 2015;23(1):14–21.

23. Tiberi S, du Plessis N, Walzl G, Vjecha MJ, Rao M, Ntoumi F, et al. Tuberculosis:
progress and advances in development of new drugs, treatment regimens, and host-
directed therapies. Lancet Infect Dis. 2018;18(7):e183–98.

24. Delogu G, Sali M, Fadda G. The biology of Mycobacterium tuberculosis infection.
Mediterr J Hematol Infect Dis. 2013;5(1):e2013070.

25. Lei B, Wei CJ, Tu SC. Action mechanism of antitubercular isoniazid: activation by
Mycobacterium tuberculosis KatG, isolation, and characterization of InhA inhibitor. J
Biol Chem. 2000;275(4):2520–6.

26. Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, et al.
Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell.
2001;104(6):901–12.

27. Jong AY, Kuo CL, Campbell JL. The CDC8 gene of yeast encodes thymidylate
kinase. J Biol Chem. 1984;259(17):11052–9.

28. Sclafani RA, Fangman WL. Yeast gene CDC8 encodes thymidylate kinase and is
complemented by herpes thymidine kinase gene TK. Proc Natl Acad Sci U S A.
1984;81(18):5821–5.

29. Ferguson FM, Gray NS. Kinase inhibitors: the road ahead. Nat Rev Drug Discov.
2018;17(7):535–77.

30. Xu C, Yang S, Jiang Z, Chen T. Protein kinase inhibitors as potential antimicrobial
drugs against tuberculosis, malaria, and HIV. Curr Pharm Des. 2017;23(29):4369–89.

31. Qi B, Li L, Huang R. Alkaloid variations within the genus Stephania
(Menispermaceae) in China. Heliyon. 2023;9(5):e16344.

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Volume 03
[if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424] 02
Received 17/05/2025
Accepted 18/06/2025
Published 29/08/2025
Retracted
Publication Time 104 Days

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